JPS6251658A - Method of racemizing carboxymethylcysteine - Google Patents

Abstract

PURPOSE:To advance recemization easily in high yield without using an aromatic aldehyde, by heating an aqueous solution of optically active S- carboxymethylcysteine in the presence of a mineral acid in a closed container at a specific temperature. CONSTITUTION:An aqueous solution of optically active S-carboxymethylcysteine (SCMC) is racemized in the presence of a mineral acid such as hydrochloric acid, etc., in a closed container at 100-140 deg.C. The concentration of the mineral acid is 0.5-2.0 equivalents/100g water, especially preferably 0.7-1.5 equivalent/100g water and the concentration of SCMC is properly 10-30wt%. L-SCMC useful as expectorant, etc., can be advantageously obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for racemizing optically active 5-carboxymethylcysteine.

B. Utilization fields of industrial production S-carboxymethyl- It is a compound useful as a phlegm.

5-Carboxymethylcysteine (hereinafter abbreviated as SCMC) can be easily synthesized from industrially inexpensive β-chloroalanine and thioglycolic acid (Japanese Patent Application Laid-Open No. 19388-1988).
7) When the raw material β-chloroalanine is optically inactive, SCMC is obtained as a DL form, and by optical resolution, L-SCM, which is very important as a pharmaceutical, can be obtained.
C can be obtained. At this time, inevitably D-SCMC
Therefore, racemization of this is of great industrial significance.

mouth. Conventional techniques and problems As a conventional technique, there is known a method of heating in an acidic aqueous medium containing an aromatic aldehyde having one hydroxyl group ortho to the aldehyde group. (
JP-A-58-167562) describes the following problems: 1. Aromatic aldehydes are expensive; 2. Due to the low water solubility of aldehydes, it is necessary to use organic solvents during racemization and SCMC recovery. 2. Recovery of aldehydes is difficult. There were many industrial disadvantages such as:

C. Means for Solving the Problems As a result of intensive studies, the present inventors found that heating an optically active SCMC aqueous solution in a closed container in the presence of a mineral acid can easily increase the concentration of SCMC without using an aromatic aldehyde. The present invention was completed by discovering that racemization progresses with good yield.

The mineral acid concentration in the present invention is 0.5 to 2.0 equivalent/10
0 g water, preferably 0.8 to 1.5 equivalents i/1
00g water. When the acid concentration is high, SCMC decomposition increases, and on the other hand, when the acid concentration is low, a sufficient racemization rate cannot be obtained.

Mineral acids include hydrochloric acid, sulfuric acid, phosphoric acid, chlorosulfonic acid,
Chlorobromic acid and the like can be used alone or in combination.

The temperature is preferably 10oN140'C. At temperatures above 140°C, SCMC decomposes frequently, and at temperatures below 100°C, racemization is slow and undesirable.

Heating is preferably carried out in a closed container in order to prevent evaporation of the acid and solvent.

There are no particular regulations regarding the SCMC concentration, but it is 10~30
'wt% is appropriate.

Heating time varies depending on the type of mineral acid and acid concentration, but
80 hours is appropriate.

2. Examples Hereinafter, the present invention will be explained in more detail with reference to Examples.
These are merely examples, and the present invention is not limited thereto.

Fruit "0 sail-".

500 mg of D-SCMC was dissolved in 2.0 g of 35% hydrochloric acid, sealed in a tube, and heated at 130° C. for 30 hours. After cooling, the tube was opened and analyzed using an optical resolution column.
There were 255 mg of MC and 229 mg of L-5CMC.

(Racemization rate 94.4%, SCMC residual rate 96.8%
) however.

Racemization rate〉 <Survival rate of SCMC> shall be.

500 mg of X1Jt-ED-5CMC was dissolved in 2.0 g of 25% hydrochloric acid, sealed, and heated at 130° C. for 70 hours. After cooling, the tube was opened and analyzed using an optical resolution column.
There were 269 mg of MC and 222 mg of L-SCMC.

(Racemization rate 90.4%, SCMC residual rate 98.1%
) g, sealed the tube, and heated at 130° C. for 50 hours.

After cooling, the tube was opened and analyzed using an optical resolution column. D-SCMC was 256 mg and L-SCMC was 226 mg.
mg was present.

(Racemization rate 93.6%, SCMC residual rate 96.3%
) 500 mg of D-3CMC was dissolved in 2.0 g of 29% hydrochloric acid, sealed in a tube, and heated at 130"C for 4 hours. After cooling, the tube was opened and analyzed using an optical resolution column. -SC
There were 250 mg of MC and 223 mg of L-SCMC.

(Racemization rate 94.5%, SCMC residual rate 94.5%
) Mitate I D-3CMCID-3C with 50% chlorosulfonic acid 2.
The mixture was dissolved at 0 g, sealed in a tube, and heated at 130'O for 20 hours. After cooling, the tube was opened and analyzed using an optical resolution column. As a result, 255 mg of D-5CMC and 228 mg of L-5CMC were present.

(Racemization; 194.5%, SCMC concentration) Survival rate 96
．． 5%)

Claims (1)

[Claims] A method for racemizing optically active S-carboxymethylcysteine, which comprises heating an optically active 5-carboxymethylcysteine aqueous solution at 100 to 140°C in a closed container in the presence of a mineral acid.